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Biomedical subjects

D Richard-Lenoble

Publications and source records attributed to D Richard-Lenoble.

At least 19 recordsLinked to original sources

In vitro activity of amphotericin B, fluconazole and voriconazole against 162 Cryptococcus neoformans isolates from Africa and Cambodia.

In order to determine the potential role that various antifungal agents might have in the management of cryptococcosis in tropical areas, the in vitro susceptibility of Cryptococcus neoformans isolates from Africa ( n=52) and Cambodia ( n=110) to three antifungal agents (amphotericin B, fluconazole and voriconazole) were compared using the E-test method. The results of this study (i) confirm the value of the E-test for testing the in vitro susceptibility of C. neoformans towards voriconazole; (ii) provide the first evidence demonstrating good activity of amphotericin B, fluconazole and voriconazole against Cambodian isolates; and (iii) show there are differences in susceptibility between African and Asian C. neoformans isolates, with Cambodian isolates appearing less susceptible to the agents tested but with amphotericin B maintaining good activity.

Africa↗

Identification and specificity of a 38 kDa Loa loa antigenic fraction in sera from high-microfilaraemic Gabonese patients.

Circulating antigens isolated from sera of three high-microfilaraemic ( Loa loa) Gabonese patients were fractionated by gel filtration. A major component (38 kDa) was identified after SDS-PAGE and immunoblotting using sera of amicrofilaraemic patients with high level of antimicrofilariae Loa loa antibodies. The 38 kDa fraction was not found in the sera of parasitised patients or healthy controls. We looked for the 38 kDa antigen in the various stages of the filarial life cycle and found it in extracts of Loa loa microfilariae but not in somatic extracts of Loa loa male and female adult worms. This fraction could be used as a diagnostic marker in loiasis for amicrofilaraemic patients.

Animals↗

Visceral leishmaniasis. Persistence of parasites in lymph nodes after clinical cure.

Visceral leishmaniasis (VL) is generally associated with severe immunodeficiency (AIDS; renal, liver, and heart transplantations; haemopoietic malignancies). More rarely it can be related to an immunotolerence status such as pregnancy. Various observations report the development of leishmaniasis several months or even years after exposure to the parasite. Relapses occur rarely in patients not known to be immunocompromised, but are common after incomplete treatment. They are frequent in patients with Leishmania/HIV co-infection. Asymptomatic phases and relapses suggest that parasite can exist in the tissues for a long time before and/or after clinical onset of the disease. The mechanisms of onset of clinical leishmaniasis following exposure and infestation are highly relevant to understanding the pathology of the disease. The survival of Leishmania parasite between infection and disease or after cure is a very important issue for clinicians and epidemiologists. We describe two cases of VL occurring in a patient with lymphoma and in a pregnant woman. In both cases, parasites remained present in the lymph nodes after clinical cure.

Adult↗

Parasitic diarrhea in normal and malnourished children.

Diarrhea is only one of the many manifestations of intestinal parasites. Environmental influences are inescapable, regardless of an individual's state of health: in a highly endemic region, intestinal parasitic colonization is almost the rule. The clinical expression of the parasitoses, however, is largely determined by host defenses; and when they are weakened, parasitic diarrhea is frequent and severe. Protein-energy malnutrition is by far the most important cause of immune deficiency in developing countries. Diarrhea caused by Strongyloides or Giardia is common and severe in malnourished children, while well-nourished children remain healthy carriers. These parasites require specific treatment in the malnourished; and the well-nourished should have preventive treatment when they are to receive corticosteroids or immunosuppressive agents. Diarrhea caused by Cryptosporidium spp. may be severe in malnourished or immunodeficient children, and recovery is achieved only after renutrition or treatment of the immunodeficiency.

Antinematodal Agents↗

[Antiparasitic treatments in pregnant women and in children in 2003].

Like antibacterial agents, antiparasite drugs for pregnant women and children must be chosen in function of the stage of pregnancy, age of the child, and expected benefit-risk ratio. While no agent is totally safe, there are few absolute contraindications. Most zones of serious endemic parasite disease are located in developing countries where parasite, bacterial, or viral conditions combined with poor nutrition treatment make it necessary to treat disease in a complex pathogenic environment that weakens pregnant women and children with multiple parasite infections. In both temperate and tropical zones, there have been few real therapeutic advances involving release of new products on the market or development of new indications for existing products. Constant appearance and extension of hematozoa resistance to conventional and even more recent antimalarial agents have prompted research to find new active drugs and long-lasting treatment combinations. Real therapeutic breakthroughs have resulted from the need to develop safe drugs without substantial side-effects for single-dose use in control programs against endemic parasite diseases in mass populations including pregnant women and young children in tropical zones. There are several notable examples in the field of major verminous diseases. Ivermectin is a versatile drug that can be used against filariasis as well as for management of intestinal worms or ectoparasitosis in temperate and tropical countries. Praziquantel is an important advance in platyhelminthiasis, especially bilharziais. Triclabendazole, the latest addition to the benzimidazole family, has shown promise as a substitute for bithionol, that is difficult to procure and not recommended in pregnant women, for treatment distomiasis occurring in pregnant women and children. Other examples include albendazole against giardiasis, nitazoxamide against cryptosporidiosis, artemisinine against bilharziasis, and paramomycine, not recommended in pregnant women, against leishmaniasis.

Adult↗

Changes in schizogony and drug response in two lines of rodent Plasmodium, P. berghei NK 65 and P. berghei ANKA.

White mice were infected with two strains, ANKA and NK 65, of Plasmodium berghei. The parasites were subjected to chloroquine pressure (60 mg/kg at each passage) during 20 passages. We then compared the behaviour of the strains as they acquired chemoresistance. The drug resistance was estimated by the 2% delay time test (D2%), and the schizogonic rhythm by the synchronicity index (SI). Before drug pressure, the ANKA strain had a D2% of 4.34, and a SI of 0.2. This strain became highly drug resistant, but synchronicity increased: the D2% was 2.93, and the SI was 0.36 at the 20th passage. The NK 65 strain had an initial D2% of 4.12, and an SI of 0.2. The chemoresistance acquired during 20 passages was very irregular for this strain: after drug pressure, the D2% was 2.03 and the SI was 0.28. Drug pressure was then removed (for both strains), for 10 passages (no chloroquine). Resistance and synchronicity returned to their initial values. The two strains behaved very differently, in terms of their affinity for reticulocytes, and with chloroquine activity which favours an increase in SI because only merozoites are preserved.

Animals↗

[Human onchocerciasis and "sowda" in the Republic of Yemen].

The geophysics of the north Yemen, associating a north-south directed mountainous fish bone (rising in more of 2,000 meters), to numerous rivers or "wadis" is convenient to the development of simulium shelters, main vectors for cutaneous filariasis to Onchocerca sp. Following several missions of bio-clinical and epidemiological evaluations in neighbouring villages of wadis, it has been possible to study different clinical aspects: one reminding the classical african onchocerciasis with generalized and diffused dermatitis, and, on an other hand, a hyperreactive dermatitis on one side of the body and associated with a collateral lymphatic ganglion. This disease is well known for local populations as "aswad" meaning "black" or "sowda". Clinically whatever the studied focus, coexists the two types of onchodermatitis (uni or bilateral). Yhe sowda patients are proportionally less numerous than those touched by the generalized type. Frequent eye lesions of the West African onchocerciasis are not found in sowda cases. In classical optical microscopy, microfilaria is morphologically indifferenciable between sowda and onchocerciasis clinical aspects. Skin snips were carried out on patients of both groups. Identification of microfilaria by molecular biology through the study of the DNA genome was done out of 5 skin snips. Microfilaria was kept dry between laminas and the DNA extracted from rehydrated microfilaria. DNA was intensified with specific primers of Onchocerca type (O150PCR). This phase was followed by hybridisation of amplification products by PCR to specific stains: OVS-2 for Onchocerca volvulus species, OCH for Onchocerca ochengi, PFS1 and PSS1-BT respectively for the forest strain and the savannah strain of Onchocerca volvulus as described previously. We can distinguish 2 kinds of answers based on the clinical origin of the snip-tests: the first one concern 3 patients with numerous dermal microfilariae but without any clinical sowda and corresponding to microfilaria O. volvulus type but different from the forest or savannah strains found in sub-Saharan Africa. The second one corresponds to 2 patients with less than 5 microfilaria in their snip-test. They show the typical clinical picture of sowda. They are identified as microfilaria type Onchocerca but they do not belong to species volvulus, or to species ochengi. It seems quite probable that the clinical picture of sowda be the result of developing onchocerciasis of animal origin and not identified as to day. The ivermectin, therapeutic of choice for African onchocerciasis in annual unique cure seems less effective in the coverage of sowda. In that case rehearsal of cures every 3 months would be necessary for mass campaigns to limit the transmission of this filariasis.

Animals↗

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

Albendazole↗

Isoenzymes of human lice: pediculus humanus and P. capitis.

Human lice (Phthiraptera: Pediculidae) from Africa, America and Europe were electrophoresed for 28 enzymes, with special interest in metabolic factors likely to be involved with insecticide resistance. Zymogram profiles of the body louse (Pediculus humanus L. from France and U.S.A.) and the head louse (P. capitis DeGeer from France, Madagascar, Mali & Senegal) were compared. Only esterase two enzymes, phosphoglucomutase (Pgm) and 3 (Est-3), showed electrophoretic variation. In our starch gel electrophoresis conditions, P. humanus showed three electromorphs of Pgm migrating anodally 6, 11 and 16 mm (designated alleles a, b, c, respectively). Of the putative Pgm alleles, b and c occurred in all samples of both species of lice, whereas allele a was found only in P. humanus lab strain from U.S.A. Esterase 3 had four electromorphs migrating 23, 26, 30 and 35 mm (designated alleles a, b, c and d). Among putative Est alleles, a was found only in P. capitis from Bamako (all 14 specimens aa homozygotes), allele d was found only in P. capitis from Dakar (39% frequency), whereas Est-3 alleles b and c showed apparently balanced polymorphism in all samples of both P. humanus and P. capitis except that from Bamako. Despite the limited amount of isoenzyme variation detected (only 2/31 polymorphic loci), divergences of Est-3 and Pgm among Pediculus populations may be relevant to their biosystematics and resistance.

Animals↗

Short- and long-term action of multiple doses of ivermectin on loiasis microfilaremia.

One hundred nine Gabonese patients infected with Loa loa microfilariae were treated with ivermectin (200 microg/kg of body weight) at the Parasitology, Mycology and Tropical Medicine Department (Faculte de Medecine et des Sciences de la Sante, Libreville, Gabon). Each was given one dose per month for six consecutive months. The peripheral blood microfilaria (mf) count before and after each dose showed an average decrease in the microfilaremia of 87.3% (short-term-single dose). An annual single-dose mass treatment with 200 microg/kg of ivermectin was sufficient to control the parasite in populations with low (< 400/ml) L. loa mf counts. One month after the sixth dose (short-term-multiple doses), the average microfilaremia rate had decreased by 99.2% compared with the initial infection (35 patients). Samples were taken from 28 patients one month after the first dose and one month after the sixth dose. The average mf count decreased by 96.4% after the first dose and by 99.6% after the sixth dose (average residual mf counts = 13.7 and 1.5 mf/ml, respectively). The mf count after the sixth dose was only 11.2% of the count after the first dose. The low mf count persisted for more than six months after the sixth treatment (long-term-multiple doses). Thus, mass treatment with multiple doses is more appropriate for areas where the blood mf count is very high. These results show that the number of the annual treatments used in mass chemotherapy with ivermectin can be adapted to each population to provide efficient protection.

Adolescent↗

[Toxoplasmosis in Dakar. Seroepidemiologic sampling of 353 women of reproductive age].

Thanks to a serological survey carried out in Dakar from January to November 1993 among 353 procreative women, immune cover regarding toxoplasmosis was assessed using ELISA methodology: 40.2% of the surveyed population had antibodies of toxoplasmosis. No evidence of age, pregnancy, number of previous pregnancies was noted in antitoxoplasmosis antibodies prevalence. The seroconversion risk seems to be low even when it has existed during pregnancy. Contamination occurred during childhood. Some sanitary education should be provided to the procreative population in order to achieve a better compliance with basic hygiene regulations during pregnancy.

Adolescent↗

[Congenital toxoplasmosis with hydrocephalus diagnosed in utero: outcome of treatment].

BACKGROUND: The neurological outcome for severe toxoplasmosis can be poor despite appropriate management. CASE REPORT: A maternal toxoplasma infection occurred at 16 weeks of amenorrhoea; prenatal diagnosis was attempted at 20 weeks, fetal infection was confirmed by mouse inoculation at the 30th week. Pyrimethamine plus sulfadiazine treatment was initiated. However, at 37 weeks of amenorrhoea, sonographic examination of the fetus detected hydrocephalus. Despite prompt ventriculo-peritoneal shunting after birth and medical treatment of toxoplasmosis, the neurological developmental outcome was complicated and prognosis is poor at 5 years of age. CONCLUSION: This case shows that parents must be carefully warned about risks of a prenatal toxoplasmosis.

Anti-Infective Agents↗

Light microscopic changes in Plasmodium falciparum from Gabonese children treated with artemether.

The changes in Plasmodium falciparum in four Gabonese children suffering from severe malaria and treated with pure artemether were observed in thin blood smears fixed and stained with Giemsa and examined by light microscopy. Peripheral blood samples were taken every 8 hr up to 72 hr from three children and every 3 hr up to 9 hr from the other child. The morphologic changes involved all development stages (trophozoites, schizonts, and gametocytes); they were first seen 3 hr after the start of treatment and all parasites were abnormal after 24 hr. After two days of treatment, all infected erythrocytes disappeared except for a few with necrotic trophozoites. The morphologic changes were similar to the ultrastructural changes previously described in vivo and in vitro in experimental models. They confirm the rapid effect of artemisinin derivatives on parasite clearance and clinical recovery, particularly in cases of cerebral malaria.

Animals↗

[Cryopreservation of isolates of Toxoplasma gondii in cell culture].

For a better preservation and identification of Toxoplasma gondii isolates, we propose a new method of freezing of toxoplasma growth in THP-1 cell culture. A cystogenic strain isolated from foetal blood has been grown in these cells and frozen in liquid nitrogen. After thawing, toxoplasma recover the same growth rate and morphology in vitro and the same capacity to form brain cysts into mice compared to the initial strains. The freezing of the cell suspension provides a simple and appropriate method for preservation of Toxoplasma gondii within "bank" isolates.

Animals↗

Detection of circulating antigens in Gabonese patients with Loa loa filariasis.

Circulating antigens were detected in sera of Gabonese patients with Loa loa filarial infection by co-electrosyneresis (Co-ES). The serum samples selected for this study were exposed to rabbit hyperimmune antifilarial antisera and human immune antisera: specific arcs were observed in 35/60 filarial patients, of whom 24/47 were microfilaraemic and 11/13 amicofilaraemic. The identity of rabbit hyperimmune antisera and loiasial immune sera was confirmed by the continuity of precipitation arcs. These preliminary studies were carried out to develop diagnostic tools for loiasis and to study the physiopathology of immune complexes.

Animals↗